Development of an antisense-based antimicrobial agent for treatment of Phytophthora capsici

Period of Performance: 05/06/2015 - 12/31/2015

$99.9K

Phase 1 SBIR

Recipient Firm

Klein Assoc., Inc.
DUBLIN, OH 43016
Firm POC
Principal Investigator

Abstract

Collectively Phytophthora species are estimated to cost the agricultur industry tens of billions of dollars per year globally. Phytophthora capsici a fungus-like plant pathogen is a scurge of vegetable crops known to infect over 45 species including peppers, cucumbers, squash, cantaloupe, watermelon, zucchini, pumpkin, eggplant, tomatoes, snap beans and lima beans.Its complex life cycle high genetic variability, sexual reproduction, and ability survive in the soll for many years makes this pathogen a nightmare for farmers. Although similar in appearance to fungi, it is an oomycete and more closely related to certain algae than fungi. Because of this most agricultural chemicals used for treating plant pathogens being designed to kill fungi, are not as effective against oomycete pathogens like P. capsici. Under idea growth conditions no chemical treatment is effective against P. capsici. When this is combined with limited success in the development of vacines against P. capsici it is clear that new control strategies are desperately needed.Guild Associates proposes to conduct proof-of-concept study to develop an antisense based agent against P. capsici. Antisense agents work by blocking the production of a target protein rather than blocking its function as most chemical agents do. Using a military analogy most cheimical treatments work like tanks engaging enemy tanks on the battle field, whereas antisense agents work like a bomber destroying the factory that makes the tanks. Our firm is currently developing a similar antisense agent for use against the fungal human pathogen Aspergillus fumigatus using similar methods. We have already identified a type of transport peptide called a cell-penetrating peptide (CPP) that is effectively transported into the fungal pathogens A.fumigatus and Candida albicans. The first part of this study will evaluate other CPPs identified from the literature against our current top CPP for their ability to be transported into P. capsici. Then the top performing transporter will be further improved using rationally designed CPP libraries to evolve an improved product. Next we will use an antisense molecule (PMO) attached to this CPP to demonstrate we can use this agent to knockdown the production of a model fluorescent protein introduced into P. capsici. Finally we will develop and test a CPP-PMO that blocks the production of protein that is essential for growth of P. capsici producing an early-stage anti-P. capsici agent. Further refinement and optimization through a Phase II grant would allow this agent to be developed into an agent ready for field testingIt is believed that through the efforts of this project, a new treatment option for P. capsici infestations in the fields of vegetable crop farmers will be attained, not borrowed from other similar looking plant pathogens, but designed and taylored specifically to eliminate P. capsici from the farms of America. Because agents of this type are the progeny of the genomics era, they can be quickly designed using the genome of the targeted pest, and since they like DNA gain meaning by the order of their component parts (similar to how words attain meaning by the order of the letters) not by a unique complex chemical structure, different agents against the same organism will have similar chemical properties reducing the amount of testing necessary to bring them to market, producing new more effective drugs quicker. Thus this project will open the door to a new age of treatment options for farmers around the world that will reduce crop losses and improve the profitability of vegetable farming.